Project Summary/Abstract Patients with end stage renal disease receiving chronic hemodialysis (HD) are disproportionately affected by the opioid epidemic. Up to two-thirds of HD patients receive opioids, three-fold higher than the general population. Moreover, opioid use in this population has been associated with a myriad of adverse outcomes including increased risk of falls, impaired cognition, hospitalization and death. To address this problem, it is of critical importance to recognize that more than one-half of HD patients experience moderate to severe pain on a regular basis, and pain control among these patients is unsatisfactory. Furthermore, a lack of rigorous evidence exists to reduce opioid dependence, and to guide management of chronic pain among HD patients. Although buprenorphine has been found to be effective in reducing opioid dependence in the general population, it has not been systematically evaluated in HD patients. Furthermore, pain management studies in HD patients have largely focused on pharmacologic therapies, reporting inconsistent findings. However, there is an urgent need to prioritize non-pharmacologic treatments for this population in view of the considerable medication burden in these patients and the narrower therapeutic window of many analgesics. The purpose of this study is to evaluate novel strategies to reduce opioid use and pain in HD patients. Specifically, we will examine the effect of non-pharmacologic (Acceptance and Commitment Therapy [ACT] and acupuncture) and pharmacologic (buprenorphine) interventions in HD patients who are receiving chronic opioid medications (>90 days/year) due to chronic pain and/or high pain interference (>3 months duration). The study will enroll 720 HD patients across 5 U.S. Hemodialysis Opioid Prescription Effort Consortium Clinical Centers. We propose to use a quantitative Sequential Multiple Assignment Randomized Trial (SMART) design with an added qualitative implementation research component so that we can evaluate adaptive interventions while responding to patients? characteristics. The specific aims of this study are to: (1) Determine the effectiveness of ACT and acupuncture as compared to the control condition in reducing opioid dose and improving pain among HD patients; (2) Identify the best adaptive intervention sequence for improved outcomes; (3) Explore age, sex, and comorbidities as potential moderators of the response to the intervention; and (4) Describe facilitators and barriers to the implementation of the intervention using in-depth, semi-structured individual interviews with intervention participants and providers. The proposed study has a strong potential for reducing opioid use and improving pain management in the HD population. Strengths of this proposal include: a) the innovative study design; b) the multidisciplinary team bringing considerable expertise in kidney disease, pain management, addiction psychiatry, and implementation science; c) established collaborative partnerships facilitating access to a large population of HD patients with a high prevalence of chronic opioid use, and d) the research team?s strong track record in recruitment and retention of kidney disease patients in large NIH-sponsored initiatives.